This competitive renewal application is directed toward continuing studies exploring hormonal regulation of CHO metabolism in the perinatal period and in the pediatric age groups, with particular emphasis on the roles of glucagon and insulin. The chronically cannulated fetal and/or newborn lamb will be used as a model for studies of fetal and neonatal production, utilization, and placental transfer of glucose, employing steady state kinetic analyses and isotopically labelled glucose under the following circumstances: normal fed state, starvation, insulin-induced hypoglycemia, exercise, infusion of glucose, glucagon, epinephrine and growth hromone to mother, and in separate studies to the fetus. Chronic long-term infusions of glucose and/or insulin directly to the fetus will be used to simulate the fetal environment of a diabetic pregnancy and to study the effects on turnover, plus placental transfer of glucose, maturation of insulin and glucagon receptors, and cardiac function, size and composition in the neonatal period. The ontogenesis of hepatic plasma membrane and cardiac receptors for glucagon and insulin will be studied in rats born to normal, diabetic or nutritionally deprived mothers. The interaction of prostaglandins or inhibitors of their biosynthesis with glucose production and with rat liver membrane receptors for glucagon and insulin will also be determined. In humans, the effects of strict metabolic control during pregnancy in insulin-dependent or gestational diabetes on amniotic fluid concentration of substrate and hormones and on neonatal glucose homeostasis will be determined. In children with insulin-dependent diabetes, the effects of once or twice daily injections of combined intermediate with short acting insulin on daily metabolic profiles and on metabolic and cardiovascular responses to standardized exercise testing will be compared. These studies we believe are logical extensions of our completed work, are based on established methodologies, and should extend knowledge and understanding of glucose homeostasis and its disorders in infants and children.